Resistance of mRNAs with AUG-proximal nonsense mutations to nonsense-mediated decay reflects variables of mRNA structure and translational activity | Zendy

Francisco J.C. Pereira | Zendy; Alexandre Teixeira | Zendy; Jian Kong | Zendy; Cristina Barbosa | Zendy; Ana Luísa Silva | Zendy; Ana Marques-Ramos | Zendy; Stephen A. Liebhaber | Zendy; Luı́sa Romão | Zendy

Open Access

Resistance of mRNAs with AUG-proximal nonsense mutations to nonsense-mediated decay reflects variables of mRNA structure and translational activity

Author(s) -

Francisco J.C. Pereira,

Alexandre Teixeira,

Jian Kong,

Cristina Barbosa,

Ana Luísa Silva,

Ana Marques-Ramos,

Stephen A. Liebhaber,

Luı́sa Romão

Publication year - 2015

Publication title -

nucleic acids research

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 9.008

H-Index - 537

eISSN - 1362-4954

pISSN - 0305-1048

DOI - 10.1093/nar/gkv588

Subject(s) - biology , nonsense mediated decay , translation (biology) , messenger rna , start codon , nonsense , genetics , eukaryotic translation , stop codon , open reading frame , ribosome , ribosomal binding site , nonsense mutation , globin , mutation , gene , peptide sequence , rna , rna splicing , missense mutation

Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that recognizes and selectively degrades mRNAs carrying premature termination codons (PTCs). The level of sensitivity of a PTC-containing mRNA to NMD is multifactorial. We have previously shown that human β-globin mRNAs carrying PTCs in close proximity to the translation initiation AUG codon escape NMD. This was called the 'AUG-proximity effect'. The present analysis of nonsense codons in the human α-globin mRNA illustrates that the determinants of the AUG-proximity effect are in fact quite complex, reflecting the ability of the ribosome to re-initiate translation 3' to the PTC and the specific sequence and secondary structure of the translated ORF. These data support a model in which the time taken to translate the short ORF, impacted by distance, sequence, and structure, not only modulates translation re-initiation, but also impacts on the exact boundary of AUG-proximity protection from NMD.

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